CKD and Its Risk Factors among Patients with Cystinuria

Abstract

Background and objectives Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP.Design, setting, participants, & measurements This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients.Results Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3-72.1) years and median diagnosis delay was 1.3 (0-45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8-70.7). Among the 314 patients aged $16 years, using the last available plasma creatinine, 22.5% had an eGFR$90 ml/min per 1.73 m 2 (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60-89, 45-59, 30-44, 15-29, and ,15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P,0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size ,10 cm in patients aged $16 years (4.39 [2.00 to 9.62]; P,0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P,0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR,60 ml/min per 1.73 m 2 (2.7 [1.5 to 5.1]; P=0.001).Conclusions CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.

Kidney stones

“…Indeed, a French cohort study of 442 patients showed that 26.7% had CKD and only 22.5% had a (normal) estimated glomerular filtration rate (eGFR) of >90 ml/min/1.73 m 2 ; a history of staghorn stones and multiple open surgical stone procedures constituted a relevant risk factor for CKD and nephrectomy 209 . Accordingly, patients should be monitored for urinary pH and volume.…”

Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria

“…In a recent UK study (16), the level of renal impairment observed was similar across all genotypes. Recently, a recent large retrospective study conducted by the French Cystinuria Group (27) showed that 5 (1.1%) of 442 patients with cystinuria progressed to end stage renal disease at a median age of 35.0 (11.8–70.7) years. Multivariate analyses revealed that progression to chronic kidney disease was associated with age, hypertension, severe damage of renal parenchymal defined as a history of partial or total nephrectomy, and so on (27).…”

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

“…Among the Third National Health and Nutrition Examination Survey (NHANES III) participants, a history of kidney stones in subjects with body mass index (BMI) ≥ 27 kg/m 2 increased the probability of having an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 compared to overweight non-stone formers [8]. Stone formers with cystinuria, uric acid or struvite stones, renal tubular acidosis, or chronic bowel disorders frequently manifest decreased GFR, and CKD/ESRD [9, 10]. Standard Roux-en-Y gastric bypass and malabsorptive types of bariatric surgery are both associated with an increased risk for stones and CKD [11].…”